Does Ketamine Have Anti-Suicidal Properties? Current Status and Future Directions

Abstract

Ketamine, a widely used anesthetic agent, is currently being investigated as a novel therapeutic for depression and suicidality. Ketamine has garnered substantial attention from researchers, clinicians, media outlets, and patients alike, but numerous questions remain. One of the compelling features of ketamine is the rapidity of its antidepressant effects, which peak just 24 hours after infusion, setting it apart from other existing treatments. Ketamine’s rapid time course has inspired research efforts to explore its potential as a life-saving therapy for patients at imminent risk of suicide. In this article, we review current evidence supporting ketamine’s rapid effects on suicidal ideation in the context of unipolar and bipolar depression. We then discuss several future directions that are necessary before ketamine can be considered as a viable treatment option for suicidality in clinical settings. These include: testing for a specific anti-suicidal effect—separate from overall antidepressant effects—to ascertain whether ketamine might hold promise for a broader class of suicidal patients; ensuring that acute benefits of ketamine can be prolonged over a clinically meaningful timeframe; and developing a better understanding of the mechanisms by which ketamine might reduce suicide risk. Such efforts will enable the field to more accurately assess ketamine’s potential, as well as its limitations, allowing for appropriate placement within the context of comprehensive clinical care for suicide prevention.

Ketamine use in current clinical practice

“…Studies to date suggest intravenous ketamine produces substantial reductions in suicidal ideation in patients with unipolar and bipolar depression, in both uncontrolled and randomized controlled trials. Large reductions have been observed in as early as 40 min post-infusion, with improvements maintained for variable amounts of time ranging from 230 min up to 10 d post-infusion [93] . Price and colleagues [94] conducted a randomized controlled trial in treatment-resistant depression, which showed that intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo.…”

Ketamine for treatment-resistant depression: recent developments and clinical applications: Table 1

“…Studies consistently show a significant decrease in SI after ketamine administration 9 27. In a review assessing ketamine's effect on suicidality in patients with TRD, single doses of ketamine decreased both depression and SI, with maintained improvement for up to 2 weeks following repeated infusions 28 27. In a study of N=14 patients with MDD experiencing SI admitted to the Emergency Room (ER), a single dose of ketamine (0.20 mg/kg) administered over 1–2 min (as opposed to the more common dose of 0.50 mg/kg administered over 40 min) reduced SI significantly when assessed 40 min postinfusion 29 27.…”

“…Suicidal ideation (SI) is among the most clinically concerning of depression, and remains a leading cause of death 26 27. A majority of studies investigating the efficacy of ketamine for depression have excluded individuals at imminent risk for suicide; however, patients with moderate degree of SI were still included.…”

“…A majority of studies investigating the efficacy of ketamine for depression have excluded individuals at imminent risk for suicide; however, patients with moderate degree of SI were still included. Studies consistently show a significant decrease in SI after ketamine administration 9 27. In a review assessing ketamine's effect on suicidality in patients with TRD, single doses of ketamine decreased both depression and SI, with maintained improvement for up to 2 weeks following repeated infusions 28 27.…”

Ketamine and suicidal ideation in depression: Jumping the gun?

“…Under such circumstances, evaluation of the potential risk-tobenefit ratio may justify a recourse to the more radical approach of using subanaesthetic dose intravenous ketamine. A number of recent reviews have explored the rapid-onset antidepressant effects of ketamine but its effect on suicidal ideation has received relatively little attention [12,13]. In this review, we showcase recent advances in neuropsychopharmacological investigations of ketamine in humans and rodents with an emphasis on the potential utility of ketamine in depressed patients with suicidal ideation.…”